The general direction of my research is to determine the organization and function of chemically-coded neuronal circuits in the dorsal horn of the spinal cord. The specific aims of this proposal are to characterize the distribution, projections and synaptology of neurotensin and met-enkephalin containing neurons in the dorsal horn. Because these peptidergic neurons occur in regions of termination of primary afferent neurons, they may modulate or mediate the transmission of sensory information through the spinal cord. Both peptides are reported to have analgetic properties, so determining the circuitry of neurons containing neurotensin and met-enkephalin will add insights into the morphologic basis for their physiological effects. The distribition of met-enkephalin neurons in the dorsal horn will be determined immunohistoochemically. Of particular interest is whether met-enkephalin perikarya exhibit periodicity in a longitudinal dimension similar to that observed for neurotensin neurons. The studies of neurotensin perikarya have indicated that a neurochemical organization exists in the rostrocaudal dimension of dorsal horn laminae that has heretofore been unappreciated. A comprehensive comparison of the distribution of neurotensin and met-enkephalin in rat and cat is also proposed. Preliminary studies indicate differences occur in the distribution of these peptides in the 2 species. Since both animals are widely used in studies of nociception and analgesia, confirmation and documentation of these differences is important. The retrograde transport of horseradish peroxidase and changes in the distribution of peptide after transection of the spinal cord will be used to determine supra-spinal, intra-segmental and intersegmental projections of spinal neurotensin and met-enkephalin neurons. Ascending projections of spinal enkephalin neurons may be important in the activation of descending systems which modulate nociception in the spinal cord. In addition, the synaptology of neurotensin-containing neurons in the superficial laminae will be characterized at the ultrastructural level. The ultrastructural studies may add insights into the morphological basis for why neurotensin is excitatory on the dorsal horn neurons and opiates are inhibitory, yet both are analgetic.